The overall goal of this project is to elucidate the cellular mechanisms involved in the modulation of tumor growth in a mouse model system. Studies have been designed to analyze the cellular interactions and receptor specificities of effector (Te) and suppressor (Ts) T cells reactive against methylcholanthrene-induced tumors in syngeneic hosts. Te cells in these systems belong to the Lyt-1+ subset. Determination of the heterogeneity of these cells for shared, unique or virus-related tumor-associated antigens will proceed by the development of a series of cloned Te cell lines. Clones will be analyzed for specificity in vitro through the use of a proliferation assay, and for efficiency in conferring protection against tumor growth in vivo. Concomitantly, attempts are being made to isolate and define the tumor antigens relevant to Te and Ts recognition. Evidence obtained thus far suggests that Te and Ts cell populations recognize distinct antigenic determinants. In keeping with data obtained in other systems, Ts cells appear to recognize native antigen and can be selectively depleted by binding to tumor cell monolayers whereas Te cell activity, as measured by in vitro proliferation to soluble tumor antigen, is macrophage dependent. Additional characterization of the suppressor network active in this tumor system revealed that the Ts1 and Ts2 populations exhibit differential specificity for antigen. Thus,the activity of Ts1 cells (or cell-derived soluble suppressive factor) can be removed by bindingto the relevant S1509a tumor cells whereas Ts2 activity is unaffected by this same absorption. Since idiotypic markers are unavailable in this system, the possible receptor specificity of Ts2for Ts1 idiotypes has not been determined. Ts cells induced by in vivo administration of anti-I-A antibodies exhibit antigen-binding characteristics similar to Ts1 and may represent a Ts1-type population. Anti-I-A antibody treatment is currently being evaluated as one therapeutic approach to the prolongation of skin graft survival. Preliminary experiments indicate that this treatment may prove beneficial in the case of grafts differing at multiple minor histocompatibility loci. The capacity of similar antibodies to interfere with the rejection of H-2-incompatible skin grafts is under investigation.